GLP-1R polymorphisms modify the relationship between exposure to gestational diabetes and offspring body mass index growth: The EPOCH study.

Objective: Exposure to maternal gestational diabetes (GDM) is associated with childhood body mass index (BMI). Among youth, we explored whether three different glucagon-like-peptide-1 receptor gene (GLP-1R) polymorphisms modified the associations between 1) GDM and BMI trajectories and 2) GDM and markers of glucose-insulin homeostasis.

Research Design and Methods: For 464 participants from the Exploring Perinatal Outcomes among CHildren (EPOCH) study, microarray genotyping was performed during childhood (~10 years). BMI trajectories across childhood and adolescence were characterized using repeated measurements from research visits and medical record abstraction. Markers of glucose-insulin homeostasis were derived from one oral glucose tolerance test in adolescence (~16 years). Linear models assessed effect modification by GLP-1R polymorphisms.

Results: Among youth with at least one minor allele of rs10305420 (CT or TT) or rs1042044 (CA or AA), but not among major allele homozygotes, exposure to GDM was associated with higher average BMI. For rs6923761, participants who were exposed to GDM and were major allele homozygotes (i.e., genotype GG) had significantly higher average BMI than all other participants in the cohort. No polymorphisms modified the association between GDM and markers of glucose-insulin homeostasis during adolescence.

Conclusions: GLP-1R polymorphisms modify the association between GDM and BMI growth among youth. Further studies are needed to replicate these findings, and to better understand the mechanisms by which GLP-1R polymorphisms lead to heterogeneity in offspring BMI growth.